Mechanisms of penicillin - vancomycine and bacitracin effect on bacteria and resistence Wednesday, the 3rd of May Industrial and food microbiology Pauline VON KORFF Félix COLLET Introduction Antibiotic drugs definition : (also called antibacterial) • Biological or synthetic substances l Micro-organisms (mould, plants) • Kill or inhibit the growth of bacteria by l 3 mechanisms : l inhibit bacterial cell wall l inhibit protein synthesis l Inhibit nucleic acid production • Not effective against viruses • Inappropriate and overuse leads to the emergence of resistent organisms • Routes of administrations : l By mouth (usually) l By injection (more severe cases) l Eyes or ear drops (cases of infection) Introduction Drug Class Mecanism of Action Penicillins Interact directly with PBPs [1] and inhibit transpeptidase activity Glycopeptides Large molecules that bind to the peptide chain of peptidoglycan (Vancomycin) subunits, blocking transglycosylation and transpeptidation Bacitracin Block transport of peptidoglycan subunits across cytoplasmic membrane [1] : Penicilline Binding Proteins Penicillin General information : • Family of becta-lactam antibiotics : group of antibiotics including penicillin G, V, procaine, penicillin and benzathine penicillin • Alexander Fleming discovered Penicillin in 1928 by serendipity • Small size, most commonly affective gram-positive but also gram- negative bacteria • Kill bacteria by weakening cell walls Penicillin Mechanism Binary fission Penicillin Resistence 1. Restrict transport Mutations in Gram-negative bacteria, fewer porins or smaller openings 2. Modify target molecules Penicillin-binding proteins 3. Enzymes beta-lactamases Vancomycine General information : • Antibiotic made by the soil bacterium Amycolatopsis orientalis • Family of glycopeptides • First sold in 1954 • Effective only on gram-positive bacteria • Kill bacteria by weakening cell walls Vancomycine mechanism Vancomycine resistence 1. Increasing thickness of the wall Mutations 2. Hyperproduction of peptidoglycan precursors Act as decoys 3. Acquisition of vancomycine VanA resistence operon Bacitracin General information : • Mixture of various polypeptide antibiotic produced by Bacillus subtilis • Bacitracin A, B1, B2, B3, F, C1, C3, E, H1, H2, H3, I1, I2 and I3 • First isolated in 1945 • Effective only on gram-positive bacteria • Kill bacteria by intering with cell wall and peptidoglycan synthesis Bacitracin mechanism ® dephosphorylation of C55 isoprenyl pyrophosphate = bactoprénol a tranport protein Bacitracin resistence 1. Protein BCRABC Bacitracin is pumped up the cell 2. Protein BACA Active phosphorylated bactoprenol from a different synthetic pathway Synthesis Antibiotic Action Target molecule drug spectrum Penicillin Gram + Transpeptidase Gram - Gram + Peptidoglycan Vancomycin Bacitracin Gram + Phosphorylase Conclusion • Antibiotics revolutionized medicine in 20th century • Bad utilisation and use in intensive animal farming are exacerbating problem with antibiotic resistence • Over 25 000 people die each year in EU from infections caused by antibiotic- resistant bacteria • Regulation and new research is needed Mechanisms of penicillin - vancomycine and bacitracin effect on bacteria and resistence Thank you for your attention, if you have any questions we would be happy to answer them. l .